Our borders can be used to create flyers, invitations, and other items. They are sized for 8.5 x 11 paper (letter size). The borders are provided in JPG and PNG (transparent) formats. These are delivered in a ZIP file. The files are 300 DPI.
Free vs. Paid Comparison
The free version includes a watermark, while the paid version doesn't. Please test the free version prior to buying to make sure it works for your intended purpose.
A download link will be sent to the email address you provide at checkout. Please make sure you enter a valid address. You should generally receive the email within a few minutes of ordering. However, please allow at least 30 minutes before contacting us about not receiving this email.
This is a digital product that you download. You will not receive a physical item via mail.
Editing the Borders
You will need software such as Microsoft Word or Photoshop to add text to the borders.
We recommend using the borders on a desktop or laptop. If you don't know how to download, edit, and print files on a phone or tablet, the learning curve is going to be steep. We are unable to assist with downloading or using the borders on a mobile device.
- Color will only print to the edge if you have a printer that supports borderless printing on 8.5 x 11 paper.
- While it is possible to add text to the borders, the borders themselves aren't editable. You can't change color, positioning of elements, etc.
- The borders are sized for 8.5 x 11 paper. They aren't intended for use with other paper sizes.
Blue On Blue Pdf Free Download Free
Blue On Blue PDF Free Download
If you purchase a premium version of a printable, you are only purchasing the files. We are unable to assist with software, troubleshooting printer issues, or anything similar. Read our support policies for more information.
Blue On Blue Pdf Free Download Windows 10
Toxic metabolic encephalopathy after parathyroidectomy with methylene blue localization Swapna S. Kartha, MD, Chris E. Chacko, Jeffrey M. Bumpous, MD, Muffin Fleming, MEd, Eric J. Lentsch, MD, and Michael B. Flynn, MD, Louisville, Kentucky OBJECTIVE: To determine the correlation between methylene blue use and toxic metabolic encephalopathy in patients undergoing surgery for primary hyperparathyroidism. STUDY DESIGN AND SETTING: A retrospective study of 193 patients was performed to collect demographic, perioperative, and postoperative data. Patients were divided into two groups: Group A (postoperative neurological sequelae) and Group B (no neurological sequelae). All data points were compared between the groups. RESULTS: Twelve of 193 patients were placed in Group A; 181 patients were placed in Group B. Ten patients in Group A were female, and 10 patients were older than 60 years. Of the patients in Group A, 100% were taking a serotonin reuptake inhibitor (SRI). In Group B, 8.8% of patients were taking an SRI. CONCLUSION: All the patients who experienced transient neurological events were taking an SRI. A correlation can be made between methylene blue infusion and SRI usage. SIGNIFICANCE: Patients taking SRIs may represent a highrisk group for postoperative neurological events when methylene blue is utilized. © 2006 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved.
With the advent of technetium sestamibi radioisotope localization for minimally invasive parathyroidectomy, the use of methylene blue as an adjunct in this context gained enthusiasm. Subsequently, reduced operative times and reduced needs for frozen section tissue confirmation further demonstrated the efficacy of methylene blue for parathyroid gland localization.4-6 Surgeons at our institution routinely used methylene blue in parathyroid gland localization in both minimally invasive radio-guided parathyroidectomy (MIRP) and standard bilateral neck exploration parathyroidectomy. A pattern of transient neurological events previously undocumented in the literature and at our institution began to emerge and became the cause of some concern, prompting the need for further investigation.
METHODS AND MEASURES
ethylene blue use for parathyroid localization was first introduced by Dudley in 1971.1 His description of safety, availability, and efficacy popularized methylene blue as an adjunct to intraoperative gland identification.2,3 Further studies demonstrated its safety up to doses of 10 mg/kg,3 with larger intravenous doses demonstrating nausea, abdominal pain, dizziness, hallucinations, and confusion.
A retrospective chart review was performed on 193 consecutive patients between January 1998 and June 2003. Every patient was enrolled in an Institutional Review Board–approved study of minimally invasive parathyroidectomy with methylene blue localization at the University of Louisville and affiliated hospitals. All charts were reviewed for demographic data, including age and gender. Historical data were also reviewed for significant medical comorbidities, medication usage, allergies, and previous surgical procedures. Primary care physicians were contacted to confirm current medication lists. Perioperative events were noted, specifi-
From the University of Louisville School of Medicine, Department of Surgery, Division of Otolaryngology (Drs Kartha, Bumpous, and Lentsch); University of Louisville School of Medicine, Department of Surgery (M. Fleming and Dr Flynn); and University of Louisville School of Medicine (C.E. Chacko).
Presented at the Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery, Los Angeles, CA, September 25-28, 2005. Reprint requests: Swapna S. Kartha, MD, 529 S. Jackson St., James Graham Brown Cancer Center, 3rd Fl., Louisville, KY 40202. E-mail address: [email protected]
0194-5998/$32.00 © 2006 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved. doi:10.1016/j.otohns.2006.05.026
Otolaryngology–Head and Neck Surgery, Vol 135, No 5, November 2006
cally preoperative medication administration by the anesthesiologist, preoperative methylene blue dosage, and sestamibi administration. Intervals between administration of methylene blue and incision were recorded. Intraoperative anesthesia records were reviewed for anesthetic agents utilized, cardiac events, and ASA class. Anesthesia for both groups was a single institution experience. The procedure performed (minimally invasive [MIRP] vs standard neck exploration), length of procedure, location of gland, and weight of gland were noted. Postoperative charts were reviewed for postoperative calcium levels and neurological events. Neurological events were defined as behavior or mental status different from the patient’s baseline as noted on their preoperative evaluation. The interval to neurological event was recorded from the time of entry to the recovery room. Patients who experienced neurological events in the first 15 minutes following arrival were defined as having immediate neurological events. The total duration of the neurological event as well as the quality/type of event was recorded (ie, confusion, vision change, somnolence, delirium). EEG findings, when performed, were also reviewed. We did not measure methemoglobin levels in either group or examine alterations in the blood-brain barrier. The 193 patients in the study were divided into two groups. Group A (n ⫽ 12) contained patients who experienced postoperative neurological sequelae. Group B (n ⫽ 181) contained patients who did not experience postoperative neurological sequelae. All data points described above were compared between Group A and Group B. t test statistical analysis for independent variables was performed for postoperative calcium levels, age, and use of serotonin reuptake inhibitors.
RESULTS A total of 193 patients were studied with methylene blue localization. Of these, 12 patients experienced postoperative neurological events and were placed in Group A. The remaining 181 patients who did not experience neurological sequelae after surgery were placed in Group B. The age range in Group A was 42 to 80 years with a mean of
Table 1 Comorbid conditions, Group A Hypertension Cardiomyopathy/coronary artery disease/ arrhythmia GERD Depression Hypothyroidism Obesity Diabetes (Types I and II) Obstructive sleep apnea Asthma Pulmonary embolism
12 8 5 4 4 4 3 3 2 1
Table 2 Medication profile of Group A Medication classification
No. of patients (of 12)
Analgesics/narcotics Beta blocker Calcium channel blocker Diuretic Neurontin Proton pump inhibitor Anti-hyperlipidemic Serotonin reuptake inhibitor
6 3 6 3 2 4 5 12
63.1 years. The age range in Group B was 14 to 83 with a mean of 58.7 years (P ⬎ 0.01). A total of 83% (10 of 12) of patients in Group A were female and 74% in Group B were female (P ⬎ 0.01). Table 1 illustrates the existing comorbid conditions in Group A. All patients in Group A had comorbid conditions that placed them in ASA class 3. Furthermore, all patients in both groups had preoperative hypercalcemia necessitating operative management of hyperparathyroidism. The medication profile of patients in Group A is demonstrated in Table 2. All patients in Group A were taking a serotonin reuptake inhibitor (SRI) as part of their daily medication regimen. In comparison with Group B, only 16 of 181 (8.8%) were taking a serotonin reuptake inhibitor (P ⬍ 0.0001). The anesthesia and medication records of all patients were reviewed and there were no significant differences in perioperative drug use or anesthetic management other than SRIs. Preoperatively, all patients in both groups received a dose of methylene blue equal to 7.5 mg/kg. All patients in Group B received preoperative sestamibi 5 minutes prior to methylene blue injection. Eleven of 12 patients received sestamibi in Group A. Injection of the dye was within 100 minutes of incision in all 193 patients. Of the patients in Group A, 7 of 12 underwent MIRP and 5 of 12 underwent standard neck exploration. The procedure lengths ranged from 34 minutes to 120 minutes. Postoperatively, 6 of the 12 patients experienced immediate (⬍15 minutes) neurological events. All patients experienced neurological symptoms in the first few hours of their postoperative period (range, immediate to 11 hours). The duration of the neurological event ranged from 1 hour to 96 hours with a mean of 35.7 hours. Table 3 lists the quality of the neurological event for each patient. No other neurological deficits, either motor or sensory, were noted. Eleven patients recovered from their neurological event without residual effect. One patient experienced cardiopulmonary arrest and subsequently died. Of the patients in Group A, 4 patients underwent an electroencephalogram (EEG). All four EEGs demonstrated toxic metabolic encephalopathy.
Kartha et al
Toxic metabolic encephalopathy after . . .
Table 3 Description of neurological events experienced by Group A Patient
1 2 3 4 5 6 7 8 9 10 11 12
confusion with blurred vision difficult to arouse confusion/delirium difficult to arouse, sluggish pupils confusion, inappropriate speech, singing confusion, agitation, weak grips confusion, vision loss confusion, tremors, hallucination confusion, jerking movements of extremities stupor/delirium, nonverbal unable to be aroused obtunded, delirium
Postoperative calcium levels were compared between Group A and Group B. The mean postoperative calcium level in Group A was 9.1 mg/dL. The mean postoperative calcium level in Group B was 9.5 mg/dL (P ⬎ 0.05).
DISCUSSION In this study, all patients who experienced neurological complications after methylene blue infusion were taking a serotonin reuptake inhibitor as part of their daily medication regimen. This is in stark contrast to the group of patients who did not experience neurological sequelae, in which only 8.8% were taking SRIs. Group A and B patients were otherwise similar and without significant differences in demographic or clinical variables. Patients in both groups were given an ASA class 3, which may have made them more vulnerable to the postoperative complications they experienced. All patients who had neurological events were presumed to have transient toxic metabolic encephalopathy, supported by EEG patterns consistent with this diagnosis in 4 documented cases. Eleven of the patients fully recovered to their baseline mental status within 4 days. One patient underwent cardiopulmonary arrest with unsuccessful resuscitation. Though this patient was unresponsive, she remained hemodynamically stable for several hours. Her comorbid condition of cardiomyopathy may have contributed to her decline, though no unusual intraoperative cardiopulmonary events were noted. No autopsy was performed on this patient to further delineate a potential cause of her death. Although confusion is not an uncommon postoperative event and there is the possibility that methylene blue and SRIs act to prolong the effects of anesthetic agents, the purpose of our study is to indicate a correlation, not establish causation. While other causal possibilities remain, such as hypoxia due to methemoglobin or alterations in the
767 blood-brain barrier, these remain speculative in this retrospective analysis. Further studies need to be performed. To date, no studies exist investigating postoperative neurological events after methylene blue use in parathyroid localization. However, 2 cases of postoperative disorientation were reported in which the patient was given methylene blue in the setting of SRI use.7,8 With these case reports and our series of patients experiencing similar events, a potential drug-drug interaction can be hypothesized. Though methylene blue has been thought to be a safe drug in low doses (5-10 mg/kg/dose), its bio-availability and ability to cross the blood-brain barrier have not been investigated in the setting of polypharmacy. Furthermore, SRIs are generally considered safe antidepressant agents and have thus gained popularity as first line in the use of depression and anxiety. This has led to subsequent increases in the number of patients taking these medications. This increase may have impacted on the pattern of patients experiencing neurological sequelae in our patients undergoing methylene blue localization as an adjunct to surgery in primary hyperparathyroidism. While a definitive drug interaction between methylene blue and SRIs cannot be established in this study, the profile of a high-risk patient can be inferred from our study that established a correlation between neurological sequelae and the use of methylene blue for parathyroid localization in patients who are taking SRIs. Use of methylene blue as a perioperative adjunct for gland localization in surgery for primary hyperparathyroidism should be avoided in patients who are concurrently taking SRIs until the safety of methylene blue is further delineated in this patient population.
CONCLUSION In our consecutive series of patients undergoing methylene blue parathyroid localization, a pattern of neurological events was noted in a subset of patients taking serotonin reuptake inhibitors. Although our study is not designed to define causation of toxic metabolic encephalopathy, it does demonstrate a strong correlation between this complication in patients who are using SRIs and receive methylene blue as a localizing in situ parathyroid tissue dye. Identifying these patients as a high-risk category, avoiding use of methylene blue in patients taking SRIs, and utilizing other means of gland localization in this group may decrease the likelihood of neurological complications. It is recommended by this group that methylene blue should not be used by patients who are using SRIs until the interaction is better defined.
REFERENCES 1. Dudley NE. Methylene blue for rapid identification of the parathyroids. BMJ 1971;3:680 –1.
Otolaryngology–Head and Neck Surgery, Vol 135, No 5, November 2006
2. Derom AF, Wallert PC, Janzing HM, et al. Intraoperative identification of parathyroid gland with methylene blue infusion. Am J Surg 1993; 165:380 –2. 3. Traynor SD, Adams JR, Anderson P, et al. Appropriate timing and velocity of infusion for the selective staining of parathyroid glands by intravenous methylene blue. Am J Surg 1998;176:15–7. 4. Orloff LA. Methylene blue and sestamibi: Complemetary tools for localizing parathyroids. Laryngoscope 2001;111:1901– 4. 5. Flynn MB, Bumpous JM, Schill K, et al. Minimally invasive radioguided parathyroidectomy. J Am Coll Surg 2000;191(1):24 –31.
6. Sackett WR, Barraclough B, Reeve TS, et al. Worldwide trends in the surgical treatment of primary hyperparathyroidism in the era of minimally invasive parathyroidectomy. Arch Surg 2002;137: 1005–59. 7. Bach KK, Lindsay FW, Berg LS, et al. Prolonged postoperative disorientation after MB infusion during parathyroidectomy. Anesth Analg 2004;99:1573– 4. 8. Martindale SJ, Stedeford JC. Neurological sequelae following methylene blue injection for parathyroidectomy. Anaesthesia 2003;58: 1041–2.